postmarketing study to evaluate add-on therapy with anticholinergics in patients with overactive bladder (oab) on mirabegron.

Conditions: Overactive Bladder (OAB)

Summary: the objective of the study was to evaluate the safety and efficacy of add-on therapy with anticholinergics in patients with oab on mirabegron.

this was a multicenter, open-label study to evaluate the safety and efficacy of add-on therapy with antimuscarinics in patients with oab treated with mirabegron. the total duration of the study period was 54 weeks in total, comprising a 2-week screening period and a 52-week treatment period. patients who met the eligibility criteria for provisional enrollment received orally the study drug for the screening period (mirabegron 50 mg) once daily after breakfast for 2 weeks. patients who met the eligibility criteria after the screening period were randomized to solifenacin 5 mg, propiverine 20 mg, imidafenacin 0.2 mg or tolterodine 4 mg in a 1:1:1:1 ratio, and received orally mirabegron 50 mg and antimuscarinics for 52 weeks. at week 8 visit, the dose of all antimuscarinics except for tolterodine could be increased by 2-fold (solifenacin 10 mg, propiverine 40 mg or imidafenacin 0.4 mg) if a patient met the following criteria: (1) had no response to the study drugs; (2) was considered by the investigator to have no safety concerns; and (3) agreed to increase the dose. however, in the event of aes after the dose was increased, it could be reduced to the level before the increase. a dose increase for a second time after dose reduction was not permitted.

Eligibility criteria:
inclusion criteria: * female: oab outpatient who had been postmenopausal for at least 1 year * male: oab outpatient who had no wish to have children in the future * patient had been under treatment with mirabegron at a stable dose of 50 mg once daily for at least 6 weeks before the start of the screening period * patient capable of walking to the bathroom without assistance * patient had a total overactive bladder symptom score (oabss) of ≥3 points and a question 3 score of ≥2 points exclusion criteria: * patient had an established diagnosis of stress urinary incontinence (patient had no symptom other than stress urinary incontinence) * patient had urinary tract infection (cystitis, prostatitis, etc.), urinary calculus (ureteric calculus, urethral calculus, bladder calculus, etc.), interstitial cystitis, or a history of recurrent urinary tract infection (at least 3 episodes within 24 weeks before the start of the screening period) * patient had a residual urine volume of ≥100 ml at week -2 visit or patient with benign prostatic hyperplasia or lower urinary tract obstruction * patient had uncontrolled hypertension (sitting systolic blood pressure ≥180 mmhg or diastolic blood pressure ≥110 mmhg at week -2 visit) * patient had a pulse rate of ≥110 bpm or \<50 bpm at week -2 visit * patient had a contraindication to antimuscarinics (urinary retention; obstruction in thepylorus, duodenum, or intestine; paralytic ileus; gastric/intestinal atony; myasthenia gravis; and decreased gastrointestinal motility/tone, etc.) * patient had glaucoma, ulcerative colitis, hyperthyroidism, dementia, cognitive dysfunction, parkinsonism symptoms, or clinically significant cerebrovascular disorder * patient had serious heart disease (myocardial infarction, cardiac failure, uncontrolled angina pectoris, serious arrhythmia, use of pacemaker, etc.), liver disease, kidney disease, immunological disease, lung disease, etc. or patient had a history of malignant tumor (except for malignant tumor that had not been treated for at least 5 years before the start of the screening period with no risk of recurrence) * patient had drug hypersensitivity to β-agonists or anticholinergics * patient was under treatment with flecainide acetate or propafenone hydrochloride * patient had long qt syndrome, patient was vulnerable to arrhythmia such as bradycardia or acute myocardial ischemia, patient had hypokalemia, and patient had ischemic heart disease such as angina pectoris * patient had used any prohibited concomitant medication within 4 weeks before the start of the screening period * patient was under catheterization or intermittent self-catheterization or patient had pelvic organ prolapse that affected the urinary tract function * patient had received radiotherapy that affected the urinary tract function * patient had received surgical therapy that may have affected the urinary tract function within 24 weeks before the start of the screening period * patient had received nonpharmacological therapy for oab such as electric stimulation therapy (interferential low frequency therapy, magnetic stimulation therapy, etc.), biofeedback therapy, bladder training, or pelvic floor muscle exercise within 2 weeks before the start of the screening period * patient had or had a history of mood disorder, neurotic disorder, and schizophrenia

Keywords: anticholinergic overactive bladder (oab) mirabegron ym178